T-cell antigen recognition requires antigen presenting cells (APCs) to present antigen fragments (peptides) on their cell surface in association with molecules of the major histocompatibility complex (MHC). T cells use their antigen specific T-cell receptors (TCRs) to recognise the antigen fragments presented by the APC. Such recognition acts as a trigger to the immune system to generate a range of responses to eradicate the antigen which has been recognised.
Recognition of external antigens by the immune system of an organism, such as man, can in some cases result in diseases, known as atopic conditions. Examples of the latter are the allergic diseases including asthma, atopic dermatitis and allergic rhinitis. In this group of diseases, B lymphocytes generate antibodies of the IgE class (in humans) which bind externally derived antigens, which are referred to in this context as allergens since these molecules elicit an allergic response. Production of allergen-specific IgE is dependent upon T lymphocytes which are also activated by (are specific for) the allergen. Allergen-specific IgE antibodies bind to the surface of cells such as basophils and mast cells by virtue of the expression by these cells of surface receptors for IgE.
Crosslinking of surface bound IgE molecules by allergen results in degranulation of these effector cells causing release of inflammatory mediators such as histamine, 5-hydroxtryptamine and lipid mediators such as the sulphidoleukotrienes. In addition to IgE-dependent events, certain allergic diseases such as asthma are characterised by IgE-independent events.
Allergic IgE-mediated diseases are currently treated with agents which provide symptomatic relief or prevention. Examples of such agents are anti-histamines, P2 agonists, and glucocorticosteroids. In addition, some IgE-mediated diseases are treated by desensitisation procedures that involve the periodic injection of allergen components or extracts. Desensitisation treatments may induce an IgG response that competes with IgE for allergen, or they may induce specific suppressor T cells that block the synthesis of IgE directed against allergen. This form of treatment is not always effective and poses the risk of provoking serious side effects, particularly general anaphylactic shock. This can be fatal unless recognised immediately and treated with adrenaline. A therapeutic treatment that would decrease or eliminate the unwanted allergic-immune response to a particular allergen, without altering the immune reactivity to other foreign antigens or triggering an allergic response itself would be of great benefit to allergic individuals.
House dust mites are universally recognised as a major cause of allergic diseases in humans and animals, including asthma, allergic rhinitis and allergic dermatitis. Two closely related species of mite are responsible for the majority of house dust mite allergy worldwide. These are Dermatophagoides pteronyssinus (predominantly in Europe) and Dermatophagoides farinae (predominantly in America). House dust mite allergens are mainly derived from proteins from the lining of the mite gut, which are present in the faeces, and are typically referred to as Der p (for D. pteronyssinus) or Der f (for D. farinae) proteins. An average mite will produce approximately 20 faecal pellets each day of its life: twice its own body weight. One gram of dust can typically contain up to 500 mites, while a mattress can hold more than two million. The amount of mite material present increases with age. One tenth of the weight of a six-year old pillow can consist of mites and mite debris. In a carpet, there will typically be between 1,000 and 10,000 mites per square meter.
Allergic diseases, particularly asthma, are a huge and expanding problem in the industrialised nations of the world. It has been calculated that 5-10% of the population of the major industrialised nations suffers from asthma. Of those, approximately one fifth will have severe asthma requiring frequent hospitalisation. The cost of asthma within the United States has been calculated as $12.6 billion (£7.9 billion) per year. Figures for Europe are even higher. A Canadian study estimated the costs of asthma as averaging £21 per year for every member of the population of the major industrialised nations. 2,000 people every year will die as a result of asthma in the United Kingdom alone.
Asthma is a chronic disease caused by allergic reactions and irritation within the respiratory system. Between 50% and 90% of asthmatics who react to airborne material are sensitive to dust mite allergens, and in one British study 10% of the general population reacted to dust mite allergens. Almost two hundred million Americans live in areas severely affected by house dust mite infestation. Sensitisation to this material occurs in childhood, mainly between three and six months of age but asthma is lifelong.
A therapeutic or preventative treatment would therefore be of great benefit to humans that suffer or are at risk of suffering from house dust mite allergy.